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V.W. Rusch



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    O22 - Mesothelioma III (ID 122)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      O22.02 - CD8 T-cell Infiltration and Tumor IL-7R Expression are Independent Prognostic Factors in Epithelioid Malignant Pleural Mesothelioma (ID 2935)

      16:15 - 17:45  |  Author(s): V.W. Rusch

      • Abstract
      • Presentation
      • Slides

      Background
      Following our publication (Cancer Immunol Immunother 2011) demonstrating the prognostic importance of chronic inflammatory cell infiltration in epithelioid malignant pleural mesothelioma (MPM), we investigated the prognostic significance of the immune microenvironment in the tumor nest and the tumor-associated stroma in epithelioid MPM.

      Methods
      A tissue microarray (TMA) was constructed from 170 epithelioid MPM cases, with 6 representative tumor cores and 3 representative stromal areas. Immunohistochemical analyses for immune cell infiltration (CD3, CD4, CD8, CD20, FoxP3) and interleukin receptors (IL-7R and IL-12Rβ2) were performed. TMA slides were analyzed for immune cell infiltration of tumor and stroma (low vs high, divided by use of the median), as well as for immune marker expression (sum of intensity and distribution). Overall survival (OS) was estimated using Kaplan-Meier analysis, and log-rank tests and Cox proportional hazards models were used to analyze the association between each marker and OS.

      Results
      Analysis of single immune cell infiltration for all patients revealed that high tumor CD8+ T-cell infiltration, high CD20+ B-cell infiltration, and low tumor IL-7R expression correlated with higher OS (Figure). Combined tumor CD8+ and CD4+ cell infiltration significantly correlated with better OS (5-year OS, 36% [n=61] vs. 20% [n=96]; p=0.008). In a multivariate analysis including age, stage, lymph node metastases, lymphatic invasion, and vascular invasion, high CD8+ T-cell infiltration and low tumor IL-7R expression were independent predictors of OS (Table). Figure 1Figure 2

      Conclusion
      Tumor CD8+ T-cell infiltration and tumor IL-7R expression are independently associated with survival, which highlights the biologic and prognostic significance of the immune microenvironment for patients with epithelioid MPM.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-003 - Spread Through Alveolar Spaces (STAS): A Newly Recognized Pattern of Invasion in Lung Adenocarcinoma Associated with Increased Recurrence in Patients Undergoing Limited Resection for ≤2cm Tumors (ID 295)

      09:30 - 16:30  |  Author(s): V.W. Rusch

      • Abstract

      Background
      We have recently demonstrated that presence of the micropapillary pattern increases the risk of local recurrence after limited resection for ≤2 cm lung adenocarcinoma (ADC). In cases of tumors with the micropapillary pattern, a detached collection of tumor cells is frequently identified within an alveolar space separate from the main tumor, which we have named “Spread Through Alveolar Spaces” (STAS). However, the prognostic significance of this finding is not known. The purpose of this study is to investigate whether the presence of STAS correlates with an increased risk of recurrence after limited resection versus lobectomy.

      Methods
      All available tumor slides from patients with therapy-naive, surgically resected solitary lung ADC ≤2 cm in size (1995-2009) were reviewed (n=697; stage IA/IB, 600/97; limited resection/lobectomy, 226/471). Comprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification. STAS was defined as isolated tumor islands (morphologically solid or micropapillary pattern) or single cells within alveolar spaces separate from the main tumor. The distance between the tumor surface and the STAS was measured by a ruler (mm) and by the number of alveolar spaces. Recurrence-free probability (RFP) was estimated using the Kaplan-Meier method.

      Results
      STAS was identified in 224 cases (32%). The morphologic types of STAS were as follows: 119 micropapillary, 91 solid, and 14 single cell. Presence of the micropapillary or solid pattern (>5%) in the main tumor and presence of lymphatic invasion were significantly associated with presence of STAS (p<0.001 for each). Presence of STAS correlated with an increased risk of recurrence (5-year RFP, 75.6%), compared with absence of STAS (5-year RFP, 83.5%; p=0.022). In the limited resection group, tumors with STAS were associated with an increased risk of recurrence, compared with those without STAS (5-year RFP, 58.3% vs 81.9%; p=0.004); this did not follow in the lobectomy group (5-year RFP, 84.1% vs 84.2%; p=0.658) (Figure). The distance between the tumor surface and the STAS did not correlate with risk of recurrence (p=0.992). Figure 1

      Conclusion
      Presence of STAS correlated with an increased risk of recurrence in patients treated with limited resection for ≤2 cm lung ADC. This finding may guide surgeons to choose lobectomy over limited resection for the treatment of these patients.